Oral Microbiome–Neuroinflammation Crosstalk: From Mechanisms to Therapeutic Modulation

The oral cavity harbors complex microbial communities whose dysbiosis has been increasingly linked to neuroinflammatory processes implicated in neurodegenerative and neuropsychiatric disorders. Periodontal pathogens and their virulence factors (e.g., lipopolysaccharide, gingipains, outer membrane vesicles) can translocate systemically, perturb blood–brain barrier integrity, activate microglia and astrocytes, and potentiate inflammasome signaling. Emerging evidence also points to bidirectional communication via peripheral immune priming, trigeminal and olfactory routes, and metabolite signaling that converge on innate immune pathways and synaptic function. Yet, causal chains, host susceptibility factors, and the relative contribution of microbial taxa, keystone pathogens, and community functions remain incompletely defined.

This Research Topic invites multidisciplinary contributions that dissect oral microbiome–brain communication across scales—from molecular effectors and cellular immunology to network-level neuroinflammation and clinical translation. We welcome mechanistic studies in cellular and animal models, high-resolution human omics (shotgun metagenomics, metatranscriptomics, metabolomics, proteomics), longitudinal and interventional cohorts, and innovative diagnostics and therapeutics targeting oral biofilms and host pathways. Submissions that integrate computational modeling, single-cell/spatial readouts, barrier biology, and systems immunology are encouraged, alongside work comparing oral and gut axes, exploring life-course exposures, and addressing reproducibility, causality, and clinical impact.

We welcome research covering topics including but not limited to:

-Mechanistic links between periodontal pathogens/virulence factors and microglial/astrocyte activation
-Oral dysbiosis, inflammation, and blood–brain barrier integrity (endothelium, pericytes, glymphatic flow)
Routes of microbial influence: hematogenous, trigeminal/olfactory, immune priming, and extracellular vesicles
-Multi-omics of the oral microbiome and host response (shotgun metagenomics, metabolomics, proteomics)
-Single-cell and spatial profiling of neuroimmune responses to oral microbial signals
-Inflammasome and TLR signaling (e.g., NLRP3, TLR2/4), cytokine networks, and synaptic consequences
-Biomarkers linking oral health to CNS outcomes; risk stratification and causal inference approaches (Mendelian randomization, mediation)
-Interventions: periodontal therapy, targeted antimicrobials, biofilm modulation, vaccines, and host-directed therapies
-Comparative analyses of oral versus gut microbiome contributions to neuroinflammation
-Translational pipelines and reproducibility standards for moving from association to mechanism to therapy

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review

Keywords: oral microbiome, neuroinflammation, periodontal disease, Porphyromonas gingivalis, gingipains, microglial activation, blood–brain barrier, NLRP3 inflammasome, lipopolysaccharide (LPS), microbiota–brain axis

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.